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Experts warn bureaucratic duplication in research ethics delaying important science

Research on human subjects is essential to the advancement of patient care. Every life-saving drug, surgical technique and medical procedure was tested at some point in its development on humans. While research on humans has yielded enormous benefits, it can also carry risks to research participants. It is therefore essential to ensure research is carried out in a safe and responsible manner.

Principles for the ethical conduct of research on humans were first formalized in the Nuremburg Code in the wake of atrocities committed by Nazi scientists during World War 2. These principles included voluntary consent from research subjects and that research not involve any unnecessary risk or harm.

However, unethical research continued well after World War 2, including long-running research such as the Tuskegee Syphilis Study, which withheld treatment for syphilis in hundreds of African American males without their voluntary consent for 25 years in order to study the progress of the disease. Abuses occurred in Canada too, including the infamous MK-ULTRA experiments carried out at the Allan Memorial Institute in Montreal during the 1950s and 1960s.

In recent decades, significant progress has been made. Regulations governing the ethical conduct of research on humans are well established and abuses are rare. All research involving human subjects in Canada receives ethical review to ensure research complies with national standards.

There is no doubt that increased compliance with ethical standards has made research safer for research subjects. However, the processes for ethical review of research were developed at a time when research was mostly carried out at a single centre. With the development of multi-centre research (research carried out in many different hospitals or settings, instead of just one), there is growing concern that the efficiency of the ethics approval process has not kept pace, and that important research is being delayed or prevented by an ethics bureaucracy plagued by inconsistent quality and needless duplication.

As multi-centre studies become an increasingly important type of research, is it time for Ontario and other jurisdictions to develop a centralized system for reviewing and ensuring the ethical conduct of research?

In order to receive funding for scientific research from these agencies, individual researchers and research institutions such as universities and academic hospitals must abide by these standards. In order to enforce the standards, institutions are required to have a Research Ethics Board (REB) to review the ethical acceptability of all research conducted by their faculty, staff and students. The policy allows small institutions to enter into formal agreements with others in their region to create regional REBs.

In some parts of Canada where health care has been regionalized, the institutions responsible for medical research are often regional health authorities, rather than individual hospitals. So to conduct research at multiple hospitals within the Capital Health region in Nova Scotia, researchers are required to receive approval from only a single REB.

Ontario, however, never fully regionalized, so hospitals remain independent research institutions. Each hospital that carries out research must therefore establish its own REB. For example, the Champlain LHIN has 16 hospitals and researchers wishing to carry out a study at multiple hospitals in this LHIN would be required to receive as many as 16 different ethics approvals.

The costs of duplication

Modern multi-centre studies can span far more than 16 hospitals. One recent study involving transportation by Emergency Medical Services in Ontario required 47 different research ethics reviews. This study only collected anonymous data from patient charts, and did not involve the testing of any new drug or medical technique. Laurie Morrison, an emergency medicine doctor at St Michael’s Hospital in Toronto and the principal investigator of this study explains that so many ethics reviews results in enormous duplication.

“You might assume there’s just a single form or process that you submit 47 times, but there isn’t. There are 47 different forms – each slightly different. 47 different conversations you need to have. 47 renewals you need each year, each with their own bureaucracy” she says.

This duplication of services comes with substantial costs, both financial and scientific.

For Morrison’s study (only one of several she operates), she had a full-time employee working for six months just to get initial ethics approval. This used up 10% of the study’s budget and does not include the additional costs of renewing ethics approval every year.

In addition to the costs imposed on researchers, each hospital conducting an ethics review may pay the members who sit on the REB (as well as the REB’s support staff). While the cost of an individual ethics review may not be large, when it is duplicated at 47 different hospitals, the costs to the system add up quickly, says Morrison.

The trouble, she notes, is that research money spent on bureaucratic duplication is money not spent on actual scientific research.

But the costs are not only financial. Michael Schull, CEO of the Institute of Clinical Evaluative Sciences (ICES), believes that scientific research in Ontario is suffering from the delays caused by unnecessary bureaucracy in the review process. “Good studies are getting delayed. They get approval from most REBs, and then get hung up by one or two REBs that want to wordsmith a consent form.” These incidents can eat up months or years of valuable research time, potentially delaying the development of life-saving treatments, he says.

Large variation in interpretation of regulations

Many of the delays created by duplication in the ethics review process are the result of variation in how ethics review regulations are interpreted, explains Sharon Freitag, director of research ethics at St. Michael’s Hospital and the former president of the Canadian Association of Research Ethics Boards.

For example, with studies involving minimal risk to research participants, REBs grant delegated review (delegated reviews are done by a small committee of the REB and are processed much faster than full reviews). However, there is large variation in how REBs interpret “minimal risk”. One researcher who spoke to Healthy Debate described a multi-centre trial in which some of the REBs who reviewed the study deemed it minimal risk and granted it delegated review. Others required full review. In those who did a full review, some approved the study with no changes, while others granted approval pending minor changes to some aspect of the study.

This researcher notes that REBs at large academic institutions that are experienced and well versed in scientific research granted the study delegated review and approved it with no changes. Full reviews and requests for changes came entirely from REBs at small institutions, usually with limited experience in scientific research.

Duplication and the resulting variation in interpretation would be justifiable if it improved safety for research participants, but Freitag is clear that “there is no evidence at all that review from 47 REBs improves patient safety.”

A better way?

National ethics standards do not actually require the duplication that has become the norm in Ontario. Section 8 of the Tri-Council Policy Statement allows for alternative ethics review processes for multi-centre trials, including review by an external, specialized or multi-centre REB, as well as through a reciprocal arrangement between REBs.

Ontario already has experience with centralized external ethics review for cancer research. The Ontario Cancer Research Ethics Board (OCREB) was created in 2003 in order to improve the quality of ethics review while also streamlining the process.

“There was a recognition that many REBs at many institutions lacked the scientific expertise to be able to provide an effective review of cancer trials,” says Janet Manzo, Executive Director of OCREB. She said this was leading to uneven quality of ethics reviews as well as substantial delays for approval. “The idea was to create a central process that could guarantee the necessary expertise to provide a rigorous ethical review, while also having only a single ethics application,” she explains.

“As a researcher, I think OCREB has been a success,” says Ralph Mayer, President of the Juravinski Hospital and Cancer Centre at Hamilton Health Sciences. “You know your research is being evaluated by people with the necessary expertise, and it’s certainly a lot more efficient.”

Alberta has had a province-wide approval system for cancer research since 2009, and is now moving to harmonize all research ethics approval for the province. “The goal is one application, one approval,” says Kathryn Todd, Senior Vice President of Research for Alberta Health Services. Todd hopes to have the harmonization agreement signed by December of 2013, at which point researchers in any area will be able to apply to a single REB for approval for a multi-centre study.

Clinical Trials Ontario is looking to implement a similar model for ethical review of clinical trials. Under this model, individual institutions will continue to have their own REBs, but responsibility for reviewing multi-centre trials will rotate between hospitals, who will take turns acting as the “board of record”. Researchers will only have to submit to a single “board of record” in order to have their research approved at all participating sites. These hospitals will share the same standards for ethical review, as well as common forms and consent letters, ensuring that the process is ethically rigorous while also relatively seamless for researchers, explains Susan Marlin, Executive Director of Clinical Trials Ontario.

Lessons learned from centralizing ethics review

Centralizing ethics review can result in significant improvements in efficiency and quality. However, Manzo is quick to point out that a great deal of work needs to be done up front in order to ensure a smooth transition.

“Centralizing is not as easy as it sounds,” she explain, “Some of the variation we see in REBs is due to different institutional cultures – a tertiary cancer hospital can have very different institutional values than a religious community hospital – these all need to be taken into account when developing common processes, forms and consent letters.

Freitag agrees, and notes that trust building is crucial to the process. “Institutions are very reluctant to let go of a process they’ve typically controlled. It takes a lot of trust to hand over responsibility for the ethical protection of your patients to another organization.” However, she also notes that a move towards centralization or rotating ethics review for multi-centre studies would not mean the elimination of local REBs. Local REBs would continue to serve the important purpose of reviewing the research of their own scientists, as well as education and fostering a culture of ethical research at their own institutions.

A careful eye to efficiency must also guide the process, says Freitag. “Any move towards a centralized or shared ethics review process needs to simplify the process, not make it more bureaucratic,” she cautions.

Moving forward

Ensuring the safety and privacy of research participants is essential. There appears to be a growing consensus, however, that the status quo of ethics review in Ontario is mired by unnecessary duplication that is delaying important research without offering any additional protection for research participants.

While any reforms to ethics review processes must first ensure rigorous protection of research participants, centralized models such as OCREB and Alberta’s harmonized system suggest protection of participants need not come at the expense of efficiency.

Should Ontario create centralized boards to review, monitor and enforce ethical conduct in research involving humans?

Enter the debate: reply to an existing comment

15 comments

Karen BurnsOctober 24th, 2013 at 10:47 am

%featured%The research ethics process should facilitate research, not hinder it.%featured%

I am conducting a large scale (150 unit) international observational study and have been struggling for over a year with ethics and contract related issues. In this low risk observational study, so far 13 rebs require surrogate consent. This will undoubtedly lead to selection bias. I can not justify the requirement for consent. Of interest 6 of these rebs are in canada. They read the same protocol…..but one requires consent while others do not? It is the same study. My concern is that the requirement for consent will undermine the validity of the data collected and therefor the study.

Moreover dealing with so many rebs over such a protracted time period has created other pragmatic problems…..for example personnel change over and centres withdraw from the study. It is a logistical nightmare. The time and energy that goes into just getting the necessary approvals …..could be better spent on implementing the protocol or designing new protocols. Grant agencies who provide funds on two or three year terms do not appreciate how difficult and time consuming it is to implement a multicentre study in the current system. The time to obtaining approval is not aligned with grant cycles and impedes study implementation.

Reform is necessary as the current process does not serve research, or science well.

Well, I hear your pain. But it’s good to know your rules too when it comes to defending your point with a REB. TCPS is very clear as to when one can be exempted from asking consent (article 3.7, 5.5 and 12.3) and so is the legal framework, though it varies from a province to another. And different countries do have different ethical guidelines and laws, naturally.

A REB has to be able to justify its decision according to the normative framework in place. And a researcher has the right to question this decision, according to that framework too.

As for your ending quote “Reform is necessary as the current process does not serve research, or science well”, it’s true. The process could be sped up. But a REB’s mandate is not to serve research, it’s to serve participants.

%featured%Another type of bureaucracy that I hear researchers grumble about a lot is contracts. Developing separate contracts with multiple centres, often for studies of minimal risk, can be very time consuming and expensive.%featured%

In addition to the duplication delays noted by Petch et al., another concern has to do with the medical orientation of most ethics approval protocols and procedures (including, still, the most recent Tri-Council statement to some extent) even when the research concerns health care issues. This is particularly the case when qualitative research is involved, which seems to confuse REBs even at some large research sites. In this regard, see for example the publications authored and edited by Will C. van den Hoonaard.

I agree with Karen, the ethics process should facilitate research, not hinder it.

A few years ago, I coordinated a cluster RCT, where we recruited about 25 hospitals across Ontario, we had to complete over 15 organizational or ethics reviews in addition to our hospital (and this was an educational telephone intervention, not even invasive!) The multi-site review issue is a big one, especially as we try to promote collaboration in research projects.

Right now, I’m working at Public Health Ontario, where we have just started piloting a new approach to ethics. We are trying to focus on facilitating and supporting, rather than compliance only. Our primary goal is to promote ethical reflection throughout the term of an entire project, rather than only at the beginning approval step for research. Many of our research admin services focus on facilitation (e.g., grant development), and I know other research admin departments are also starting to move in this direction as well. One of the key things we decided to do was to develop ethics support services beyond review. We launched an advisory service, a series of educational pieces, and have developed a couple of innovative tools to help streamline our review procedures. We are still in the early days now, but the biggest challenge is balancing a streamlined approach, with TCPS 2 requirements. We are pushing the envelope, with big support from our senior management and ethics board Chair, but it is definitely a challenge to get the balance of support and streamlined approaches vs. compliance expectations right.

Ross Upshur wrote a piece a couple of years ago, noting that while there is certainly room for improving ethics review, we also have to acknowledge the significant delays that arise from processes associated with funding and publication. (Upshur REG. Ask not what your REB can do for you; ask what you can do for your REB. Can Fam Physician 2011;57:1113-4, 1115-7. (Eng),. (Fr).)

%featured%Where processes or standards have become too onerous, I think some of the blame comes from our reactions when a research study goes amiss. There is a tendency to hang the REB out to dry—dissecting consent forms for what was missing and commenting on the laxity of review or process. This promotes a “more is better” (or at least safer) approach to research ethics%featured%, with many REB members pre-occupied with not missing something, lest they be the next example. It takes a certain amount of courage to facilitate research by truly adopting a proportionate approach to ethics review processes and requirements, particularly regarding consent.

Boohoohoo! You experienced research and REB as a resident (aka no formal training in research) and think you have a point? It’s like an undergrad student saying he’s not going for a master’s because of ethics.

This doesn’t have to be an ‘either/or’ debate on efficiency. Four organizations in Toronto have created a Joint Research Ethics Board (Bridgepoint Health, Toronto Central CCAC, Toronto Grace, and West Park Healthcare Centre). We share the costs and support structure (including a research secretariat and research database) for running our JREB and have hired a professional Chair. Not only has this process streamlined our ethics approval processes and lowered our costs, it has created natural opportunities for research collaboration across our organizations. There are innovative ways to find a middle ground.

As a non-medical, qualitative researcher who has spent the last twenty-five years doing health policy research, I find that applying the same standards and requirements to conducting interviews with health care bureaucrats and policy advocates as are required for RCTs show a fundamental lack of understanding of the the logistics and risks associated with different forms of research. Research ethics and contract research at universities have become a runaway bureaucratic train designed to ensure corporate risk management (cover the potential legal liability of universities). If the trend continues, eventually researchers will need to hire contract and other types of lawyers to represent them in the process. Many researchers now require large teams of soft-funded staff just to deal with the growing bureaucratic weight attached to research funding. I guess lawyers will just be the next skill set to be added to the staffing complement. Saints preserve us!

The duplication of review processes across different hospitals (and indeed regions of Canada) is unnecessary. Central review bodies such as OCREB should serve as models for national ones — they bring the highest quality of review and the most experienced and qualified reviewers to the process improving speed, efficiency and reducing costs tremendously.

I respectfully disagree with the poll question, and the assertion (explicit or implicit) in the article that since there is no evidence that additional REB reviews improve patient safety, this justifies a move to substantially reduce the number of REBs reviewing multi-site research studies in Ontario.

There is no evidence of this, because it isn’t possible to gather evidence of this. My video response can be found below, but I am happy to write an article outlining my objections to top-down streamlining of research ethics reviews as the ideal, or even preferred solution to slow research ethics review timelines for multi-site research studies.

Of note, Dr. Greg Koski, former director of OHRP (U.S. regulator of human subjects research) gave a presentation at a CAREB Conference in 2011 where he shared a similar viewpoint re: the inability or at least the extreme difficulty of gathering evidence to demonstrate that additional REB reviews add to the safety of research participants. The analogy he used was of increased airport security since September 2001 and the lack of evidence that it adds to flight passenger safety. Despite this lack of evidence, it is intuitive that less airport security can lead to real risks to flight passenger safety. I can’t do justice to his excellent presentation here in limited comment space, but hopefully the slides or a video of the presentation are available online somewhere.

This document is provided under the terms of a CreativeCommons Attribution Non-commercial Share Alike license. The terms of the license are available at: http://creativecommons.org/licenses/by-nc-sa/3.0/. Attributions are to be made to HealthyDebate.ca, a project under the direction of Dr. Andreas Laupacis, at the Keenan Research Centre, Li Ka Shing Knowledge Institute of St. Michael’s Hospital.